Literature DB >> 22719471

N-(1-Acetyl-5-benzoyl-1,4,5,6-tetra-hydro-pyrrolo-[3,4-c]pyrazol-3-yl)benzamide.

Xiao-Guang Bai1, Ju-Xian Wang, Yu-Cheng Wang.   

Abstract

In the mol-ecule of the title compound, C(21)H(18)N(4)O(3), the fused pyrrolo-[3,4-c]pyrazole ring system is approximately planar [maximum deviation = 0.0486 (16) Å] and forms dihedral angles of 87.21 (8) and 35.46 (7)° with the phenyl rings. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds and weak C-H⋯π inter-actions link the mol-ecules into chains parallel to [201].

Entities:  

Year:  2012        PMID： 22719471      PMCID： PMC3379273          DOI： 10.1107/S1600536812019708

Source DB:  PubMed          Journal:  Acta Crystallogr Sect E Struct Rep Online        ISSN： 1600-5368


Related literature

For background to potential anti­cancer kinase inhibitors, see: Fancelli et al. (2005 ▶); Gadekar et al. (1968 ▶). For the structures of related compounds synthesized by our group, see: Guo et al. (2010 ▶); Xia et al. (2011 ▶).

Experimental

Crystal data

C21H18N4O3 M = 374.39 Monoclinic, a = 5.32163 (11) Å b = 21.1878 (5) Å c = 16.4585 (3) Å β = 96.9378 (17)° V = 1842.16 (7) Å3 Z = 4 Cu Kα radiation μ = 0.76 mm−1 T = 293 K 0.25 × 0.22 × 0.18 mm

Data collection

Oxford Diffraction Xcalibur Atlas Gemini ultra diffractometer Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T min = 0.819, T max = 1.000 10256 measured reflections 3276 independent reflections 2856 reflections with I > 2σ(I) R int = 0.018

Refinement

R[F 2 > 2σ(F 2)] = 0.053 wR(F 2) = 0.150 S = 1.07 3276 reflections 254 parameters H-atom parameters constrained Δρmax = 0.62 e Å−3 Δρmin = −0.25 e Å−3 Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL. Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812019708/rz2745sup1.cif Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812019708/rz2745Isup2.hkl Supplementary material file. DOI: 10.1107/S1600536812019708/rz2745Isup3.cml Additional supplementary materials: crystallographic information; 3D view; checkCIF report
C21H18N4O3F(000) = 784
Mr = 374.39Dx = 1.350 Mg m−3
Monoclinic, P21/cCu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2ybcCell parameters from 5825 reflections
a = 5.32163 (11) Åθ = 3.4–66.8°
b = 21.1878 (5) ŵ = 0.76 mm−1
c = 16.4585 (3) ÅT = 293 K
β = 96.9378 (17)°Block, colorless
V = 1842.16 (7) Å30.25 × 0.22 × 0.18 mm
Z = 4
Oxford Diffraction Xcalibur Atlas Gemini ultra diffractometer3276 independent reflections
Radiation source: Enhance Ultra (Cu) X-ray Source2856 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.018
Detector resolution: 10.4713 pixels mm-1θmax = 66.9°, θmin = 3.4°
ω scansh = −6→5
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)k = −25→23
Tmin = 0.819, Tmax = 1.000l = −19→18
10256 measured reflections
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.053Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.150H-atom parameters constrained
S = 1.07w = 1/[σ2(Fo2) + (0.0752P)2 + 0.8604P] where P = (Fo2 + 2Fc2)/3
3276 reflections(Δ/σ)max < 0.001
254 parametersΔρmax = 0.62 e Å−3
0 restraintsΔρmin = −0.25 e Å−3
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
xyzUiso*/Ueq
O1−0.5691 (3)0.31747 (7)0.32789 (9)0.0590 (4)
N40.3203 (3)0.24185 (8)0.66211 (9)0.0422 (4)
H40.39040.21610.69830.051*
N3−0.3129 (3)0.29957 (8)0.44421 (10)0.0421 (4)
N20.0354 (3)0.16211 (8)0.61696 (10)0.0481 (4)
N1−0.1782 (3)0.15647 (8)0.56051 (10)0.0459 (4)
O20.3492 (4)0.33753 (8)0.60417 (11)0.0722 (6)
C8−0.3981 (4)0.33561 (9)0.37999 (11)0.0421 (4)
C30.1126 (3)0.22096 (9)0.60959 (10)0.0380 (4)
C1−0.2243 (4)0.21181 (9)0.51951 (11)0.0387 (4)
O3−0.5009 (4)0.10010 (8)0.49746 (12)0.0764 (6)
C2−0.0472 (3)0.25406 (9)0.54786 (10)0.0370 (4)
C5−0.4179 (4)0.23584 (9)0.45428 (11)0.0413 (4)
H5A−0.42400.21110.40450.050*
H5B−0.58500.23750.47210.050*
C4−0.0927 (4)0.31603 (9)0.50527 (12)0.0449 (5)
H4A−0.13510.34880.54250.054*
H4B0.05220.32920.47900.054*
C150.4185 (4)0.30113 (9)0.65912 (12)0.0446 (5)
C210.8086 (4)0.27803 (11)0.75721 (12)0.0471 (5)
H210.80900.23660.73840.057*
C160.6190 (4)0.31905 (9)0.72611 (11)0.0425 (4)
C9−0.2769 (4)0.39859 (9)0.37409 (12)0.0456 (5)
C170.6176 (4)0.38031 (11)0.75652 (14)0.0562 (6)
H170.49120.40830.73590.067*
C200.9981 (4)0.29859 (13)0.81639 (14)0.0600 (6)
H201.12830.27130.83600.072*
C6−0.3162 (5)0.10024 (11)0.54676 (15)0.0661 (7)
C180.8033 (5)0.39953 (12)0.81712 (16)0.0663 (7)
H180.79870.44010.83840.080*
C190.9951 (4)0.35908 (14)0.84631 (15)0.0658 (7)
H191.12250.37260.88620.079*
C12−0.0648 (6)0.51684 (12)0.35967 (17)0.0757 (8)
H120.00220.55680.35310.091*
C14−0.0915 (6)0.40756 (13)0.3251 (2)0.0800 (8)
H14−0.03710.37380.29550.096*
C10−0.3456 (8)0.44917 (14)0.4169 (2)0.1090 (14)
H10−0.46670.44400.45260.131*
C7−0.2147 (10)0.04482 (15)0.5952 (3)0.144 (2)
H7A−0.03540.04180.59330.216*
H7B−0.29550.00710.57270.216*
H7C−0.24730.04960.65100.216*
C11−0.2405 (10)0.50798 (14)0.4088 (3)0.1191 (16)
H11−0.29400.54180.43830.143*
C130.0164 (7)0.46637 (15)0.3188 (2)0.0912 (10)
H130.14620.47160.28630.109*
U11U22U33U12U13U23
O10.0642 (10)0.0544 (9)0.0505 (8)0.0047 (7)−0.0257 (7)−0.0032 (7)
N40.0440 (9)0.0414 (9)0.0372 (8)−0.0003 (7)−0.0114 (7)0.0038 (6)
N30.0397 (8)0.0425 (9)0.0404 (8)−0.0025 (6)−0.0106 (7)0.0033 (7)
N20.0570 (10)0.0412 (9)0.0413 (9)−0.0033 (7)−0.0135 (7)0.0027 (7)
N10.0542 (10)0.0384 (9)0.0410 (9)−0.0075 (7)−0.0103 (7)0.0016 (7)
O20.0808 (12)0.0558 (10)0.0684 (11)−0.0185 (8)−0.0383 (9)0.0207 (8)
C80.0409 (10)0.0441 (10)0.0385 (9)0.0099 (8)−0.0066 (8)−0.0028 (8)
C30.0415 (10)0.0392 (10)0.0312 (9)0.0001 (8)−0.0037 (7)−0.0005 (7)
C10.0408 (10)0.0405 (10)0.0332 (9)−0.0033 (8)−0.0025 (7)−0.0009 (7)
O30.0830 (12)0.0615 (11)0.0758 (11)−0.0270 (9)−0.0268 (10)0.0046 (9)
C20.0382 (9)0.0390 (9)0.0320 (9)−0.0013 (7)−0.0032 (7)0.0001 (7)
C50.0388 (10)0.0436 (10)0.0393 (10)−0.0039 (8)−0.0042 (8)−0.0007 (8)
C40.0438 (10)0.0424 (10)0.0439 (10)−0.0044 (8)−0.0140 (8)0.0051 (8)
C150.0432 (11)0.0447 (11)0.0424 (10)−0.0015 (8)−0.0097 (8)0.0029 (8)
C210.0381 (10)0.0599 (12)0.0422 (10)0.0033 (9)0.0002 (8)0.0017 (9)
C160.0373 (10)0.0487 (11)0.0393 (10)−0.0054 (8)−0.0039 (8)0.0027 (8)
C90.0526 (11)0.0414 (10)0.0387 (10)0.0096 (8)−0.0109 (8)0.0033 (8)
C170.0543 (12)0.0482 (12)0.0616 (13)−0.0054 (10)−0.0119 (10)0.0011 (10)
C200.0346 (11)0.0916 (18)0.0508 (12)0.0024 (11)−0.0067 (9)0.0084 (12)
C60.0853 (17)0.0459 (13)0.0605 (14)−0.0183 (12)−0.0185 (13)0.0035 (10)
C180.0727 (16)0.0577 (14)0.0636 (14)−0.0207 (12)−0.0114 (12)−0.0061 (11)
C190.0480 (13)0.0912 (19)0.0534 (13)−0.0250 (12)−0.0130 (10)0.0008 (12)
C120.109 (2)0.0471 (14)0.0671 (16)−0.0103 (14)−0.0054 (15)0.0079 (12)
C140.0849 (19)0.0602 (16)0.100 (2)−0.0115 (13)0.0312 (17)−0.0197 (14)
C100.171 (4)0.0469 (15)0.127 (3)−0.0042 (18)0.093 (3)−0.0123 (16)
C70.198 (5)0.0529 (18)0.153 (4)−0.045 (2)−0.095 (3)0.036 (2)
C110.201 (4)0.0424 (15)0.130 (3)−0.001 (2)0.085 (3)−0.0123 (17)
C130.101 (2)0.076 (2)0.102 (2)−0.0246 (17)0.0325 (19)−0.0060 (17)
O1—C81.234 (2)C21—H210.9300
N4—C151.364 (3)C16—C171.391 (3)
N4—C31.391 (2)C9—C101.357 (3)
N4—H40.8600C9—C141.361 (4)
N3—C81.338 (2)C17—C181.378 (3)
N3—C51.478 (2)C17—H170.9300
N3—C41.490 (2)C20—C191.374 (4)
N2—C31.323 (2)C20—H200.9300
N2—N11.384 (2)C6—C71.484 (4)
N1—C11.360 (2)C18—C191.374 (4)
N1—C61.403 (3)C18—H180.9300
O2—C151.212 (2)C19—H190.9300
C8—C91.490 (3)C12—C111.322 (5)
C3—C21.428 (2)C12—C131.361 (4)
C1—C21.342 (3)C12—H120.9300
C1—C51.485 (2)C14—C131.381 (4)
O3—C61.197 (3)C14—H140.9300
C2—C41.494 (3)C10—C111.379 (5)
C5—H5A0.9700C10—H100.9300
C5—H5B0.9700C7—H7A0.9600
C4—H4A0.9700C7—H7B0.9600
C4—H4B0.9700C7—H7C0.9600
C15—C161.488 (3)C11—H110.9300
C21—C161.382 (3)C13—H130.9300
C21—C201.385 (3)
C15—N4—C3123.38 (15)C21—C16—C15122.68 (19)
C15—N4—H4118.3C17—C16—C15118.04 (18)
C3—N4—H4118.3C10—C9—C14117.2 (2)
C8—N3—C5120.87 (15)C10—C9—C8121.8 (2)
C8—N3—C4124.28 (16)C14—C9—C8120.9 (2)
C5—N3—C4114.54 (14)C18—C17—C16120.1 (2)
C3—N2—N1105.01 (15)C18—C17—H17119.9
C1—N1—N2110.03 (15)C16—C17—H17119.9
C1—N1—C6126.34 (17)C19—C20—C21120.4 (2)
N2—N1—C6123.57 (17)C19—C20—H20119.8
O1—C8—N3121.50 (19)C21—C20—H20119.8
O1—C8—C9121.48 (17)O3—C6—N1118.8 (2)
N3—C8—C9117.02 (16)O3—C6—C7125.3 (2)
N2—C3—N4118.38 (16)N1—C6—C7115.8 (2)
N2—C3—C2111.31 (16)C19—C18—C17120.4 (2)
N4—C3—C2130.26 (17)C19—C18—H18119.8
C2—C1—N1109.02 (16)C17—C18—H18119.8
C2—C1—C5114.80 (17)C20—C19—C18119.8 (2)
N1—C1—C5136.18 (17)C20—C19—H19120.1
C1—C2—C3104.63 (16)C18—C19—H19120.1
C1—C2—C4110.84 (16)C11—C12—C13118.8 (3)
C3—C2—C4144.53 (17)C11—C12—H12120.6
N3—C5—C198.93 (14)C13—C12—H12120.6
N3—C5—H5A112.0C9—C14—C13120.5 (3)
C1—C5—H5A112.0C9—C14—H14119.7
N3—C5—H5B112.0C13—C14—H14119.7
C1—C5—H5B112.0C9—C10—C11121.7 (3)
H5A—C5—H5B109.7C9—C10—H10119.1
N3—C4—C2100.40 (15)C11—C10—H10119.1
N3—C4—H4A111.7C6—C7—H7A109.5
C2—C4—H4A111.7C6—C7—H7B109.5
N3—C4—H4B111.7H7A—C7—H7B109.5
C2—C4—H4B111.7C6—C7—H7C109.5
H4A—C4—H4B109.5H7A—C7—H7C109.5
O2—C15—N4121.98 (17)H7B—C7—H7C109.5
O2—C15—C16121.14 (18)C12—C11—C10120.8 (3)
N4—C15—C16116.88 (16)C12—C11—H11119.6
C16—C21—C20120.0 (2)C10—C11—H11119.6
C16—C21—H21120.0C12—C13—C14120.8 (3)
C20—C21—H21120.0C12—C13—H13119.6
C21—C16—C17119.25 (18)C14—C13—H13119.6
C3—N2—N1—C10.7 (2)C3—N4—C15—O2−8.7 (3)
C3—N2—N1—C6178.1 (2)C3—N4—C15—C16172.23 (17)
C5—N3—C8—O11.1 (3)C20—C21—C16—C17−1.7 (3)
C4—N3—C8—O1174.41 (19)C20—C21—C16—C15176.36 (19)
C5—N3—C8—C9−178.70 (17)O2—C15—C16—C21−138.6 (2)
C4—N3—C8—C9−5.4 (3)N4—C15—C16—C2140.5 (3)
N1—N2—C3—N4176.94 (16)O2—C15—C16—C1739.5 (3)
N1—N2—C3—C2−0.7 (2)N4—C15—C16—C17−141.4 (2)
C15—N4—C3—N2178.88 (19)O1—C8—C9—C1098.7 (3)
C15—N4—C3—C2−4.0 (3)N3—C8—C9—C10−81.5 (3)
N2—N1—C1—C2−0.4 (2)O1—C8—C9—C14−81.3 (3)
C6—N1—C1—C2−177.8 (2)N3—C8—C9—C1498.5 (3)
N2—N1—C1—C5−179.4 (2)C21—C16—C17—C18−0.2 (3)
C6—N1—C1—C53.2 (4)C15—C16—C17—C18−178.4 (2)
N1—C1—C2—C30.0 (2)C16—C21—C20—C191.9 (3)
C5—C1—C2—C3179.24 (16)C1—N1—C6—O3−4.1 (4)
N1—C1—C2—C4−179.16 (17)N2—N1—C6—O3178.9 (2)
C5—C1—C2—C40.1 (2)C1—N1—C6—C7175.1 (3)
N2—C3—C2—C10.5 (2)N2—N1—C6—C7−1.9 (4)
N4—C3—C2—C1−176.80 (19)C16—C17—C18—C191.9 (4)
N2—C3—C2—C4179.1 (3)C21—C20—C19—C18−0.2 (4)
N4—C3—C2—C41.8 (4)C17—C18—C19—C20−1.7 (4)
C8—N3—C5—C1167.03 (17)C10—C9—C14—C13−1.2 (5)
C4—N3—C5—C1−6.9 (2)C8—C9—C14—C13178.8 (3)
C2—C1—C5—N34.0 (2)C14—C9—C10—C112.7 (6)
N1—C1—C5—N3−177.0 (2)C8—C9—C10—C11−177.3 (4)
C8—N3—C4—C2−166.62 (18)C13—C12—C11—C10−1.9 (7)
C5—N3—C4—C27.0 (2)C9—C10—C11—C12−1.1 (7)
C1—C2—C4—N3−4.1 (2)C11—C12—C13—C143.3 (6)
C3—C2—C4—N3177.3 (3)C9—C14—C13—C12−1.8 (5)
D—H···AD—HH···AD···AD—H···A
N4—H4···O1i0.862.232.997 (2)148
C20—H20···O1ii0.932.493.359 (3)156
C5—H5A···Cg1ii0.972.643.508 (3)150
Table 1

Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C16–C21 phenyl ring.

D—H⋯AD—HH⋯AD⋯AD—H⋯A
N4—H4⋯O1i0.862.232.997 (2)148
C20—H20⋯O1ii0.932.493.359 (3)156
C5—H5A⋯Cg1ii0.972.643.508 (3)150

Symmetry codes: (i) ; (ii) .

  5 in total

1.  Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition.

Authors:  Daniele Fancelli; Daniela Berta; Simona Bindi; Alexander Cameron; Paolo Cappella; Patrizia Carpinelli; Cornel Catana; Barbara Forte; Patrizia Giordano; Maria Laura Giorgini; Sergio Mantegani; Aurelio Marsiglio; Maurizio Meroni; Juergen Moll; Valeria Pittalà; Fulvia Roletto; Dino Severino; Chiara Soncini; Paola Storici; Roberto Tonani; Mario Varasi; Anna Vulpetti; Paola Vianello
Journal:  J Med Chem       Date:  2005-04-21       Impact factor: 7.446

2.  A short history of SHELX.

Authors:  George M Sheldrick
Journal:  Acta Crystallogr A       Date:  2007-12-21       Impact factor: 2.290

3.  Dihydropyrrolo[3,4-c]pyrazoles.

Authors:  S M Gadekar; B D Johnson; E Cohen
Journal:  J Med Chem       Date:  1968-05       Impact factor: 7.446

4.  tert-Butyl 3-amino-2-methyl-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxyl-ate.

Authors:  Xin Guo; Xiao Guang Bai; Yi Liang Li; Yu Cheng Wang
Journal:  Acta Crystallogr Sect E Struct Rep Online       Date:  2010-04-17

5.  5-tert-Butyl 1-ethyl 3-amino-1,4,5,6-tetra-hydro-pyrrolo-[3,4-c]pyrazole-1,5-dicarboxyl-ate.

Authors:  Wen-Bin Xia; Xiao-Guang Bai; Hong-Tao Liu; Ju-Xian Wang
Journal:  Acta Crystallogr Sect E Struct Rep Online       Date:  2011-04-16
  5 in total

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